The purpose of the project is to study the mechanisms involved in regulating the binding of oxygen to hemoglobin and the transport of oxygen to the tissues. The project also focuses on ways in which these functions are impaired and change with age. We have also studied the mechanisms involved in the oxidation of hemoglobin. Oxidation effects oxygen transport because it produces nonfunctional hemoglobin, which no longer binds oxygen. We have extended these studies to include an investigation of the stability of the erythrocyte as measured by osmotic fragility and rates of hemolysis. Changes in these parameters have been observed as a function of age and studies have been initiated to explain the origin of these age-related changes.